Ataxia telangiectasia (AT) is a multi-faceted autosomal disease in which homozygous affected individuals have high cancer rates and extreme radiation sensitivity. Although the AT disease is a rare entity, AT heterozygotes may constitute an estimated 1.4% of the population, and show a familial disposition to breast cancer. Furthermore, epidemiological studies by Swift have suggested more than 7% of patients with breast cancer may be heterozygotes for ATM. Patients who are heterozygotes for ATM may be more sensitive to exposure to high doses of ionizing radiation, constituting a subpopulation at risk for radiation complications. Positional cloning has recently yielded the (ATM) gene sequence that is mutated in AT patients, opening a tremendous opportunity to experimentally address questions on the role of ATM in breast cancer epidemiology, and its significance to diagnostic and therapeutic ionizing radiation used in breast cancer patients. We propose to evaluate the presence of a mutated gene (ATM) in a prospective clinical trial of 200 patients undergoing radiation therapy to the breast for carcinoma. We will monitor acute skin reactions, and identify ATM mutations using RT-PCR, SSCP, PTT and sequence analysis. We will correlate clinical observations to molecular findings to provide evidence in support or against the hypotheses that (1) AT heterozygotes comprise a more "radiation sensitive" cohort of patients, and (2) that patients with breast cancer have a higher incidence of AT heterozygosity. Furthermore, a positive correlation of ATM mutations to acute radiation reactions will form the basis for ATM as a possible predictive assay for breast cancer patients undergoing diagnostic and therapeutic radiation applications.